Chitosan/Alginate Nanoparticles with Sustained Release of Esculentoside A for Burn Wound Healing

Abstract

Burn injury remains one of the most devastating burdens on global public health. The inflammation, caused by burn injury and transplantation of dermal scaffolds, often leads to delayed burn wound healing. Esculentoside A (EsA), with a strong anti-inflammatory capacity, is an available agent that might contribute to the treatment of burn wounds. However, the poor stability and toxicity of EsA limit its clinical application. In the present study, we constructed chitosan/alginate nanoparticles (EsA-CS/ALG-NPs) to improve sustainability and reduce toxicity followed by impregnation of the prepared EsA-CS/ALG-NPs into a collagen/chitosan scaffold (EsA-CS/ALG-NPs@CCS). The particle size, structural morphology, thermal properties, and chemical interaction of repaired nanoparticles were evaluated using the Nanometrics instrument, differential scanning calorimetry, transmission electron microscopy, and Fourier transform infrared spectroscopy, respectively. The hybrid EsA-CS/ALG-NPs@CCS was evaluated for physical characteristics, in vitro drug release, biocompatibility, and anti-inflammation capacity with RAW 264.7 cells and in vivo burn wound healing studies with SD rats. The results showed that we successfully constructed CS/ALG-NPs and optimized the preparation process to achieve the highest encapsulation efficiency. The hybrid EsA-CS/ALG-NPs@CCS, with reduced cytotoxicity and sustained release of EsA, could alleviate inflammation, decrease the ratio of M1 macrophages, and increase the proportion of M2 macrophages in vitro. It was demonstrated that 5 μg EsA CS/ALG-NPs@CCS not only reduces inflammatory cytokines secretion and inhibits M1 macrophages but also promotes the release of anti-inflammatory cytokines and activates M2 macrophages, thereby achieving accelerated and high-quality healing of burn wounds ultimately. In summary, our work suggests that the synergistic combination of EsA, nanoparticles, and scaffolds provided a promising strategy for treating burn injuries.

Biodegradable Biopolymeric Nanoparticles for Biomedical Applications-Challenges and Future Outlook

“…Drug concentrations in the nanocomposite scaffold showed better healing properties than the blank scaffold. The wound was almost completely healed at the end of day 21 [ 95 ].…”

“… Images of the healing of burn wounds after transplantation with the blank Collagen/chitosan scaffold, 5 μg drug–chitosan/alginate nanoparticles @ collagen/chitosan scaffold, 10 μg drug-chitosan/alginate nanoparticles @collagen/chitosan scaffold, and blank collagen chitosan scaffold with 5 μg drug at days 0, 3, 7, 14, and 21 (Reproduced with permission from [ 95 ]; Copyright 2023, American Chemical Society). …”

Material and Design Toolkit for Drug Delivery: State of the Art, Trends, and Challenges

“…(a) Sustained release of esculentoside A from chitosan/alginate NPS into a collagen/chitosan scaffold (CCS) for burn wound healing. Reproduced with permission from ref . Copyright 2023 American Chemical Society.…”

Chitosan-insulin nano-formulations as critical modulators of inflammatory cytokines and Nrf-2 pathway to accelerate burn wound healing

“…The hydrogel films were developed using carboxy methyl chitosan and hydroxyethyl cellulose for potent fibroblast growth factor-2 (FGF-2) delivery to the dermal tissue injury site [ 56 ]. Similarly, chitosan/alginate nanoparticles were used to heal burn wounds by delivering Esculentoside A at the burn site [ 57 ]. The present study aims to synthesize insulin-loaded chitosan nano-formulations and investigate human insulin's structural and functional changes after interaction with chitosan under various physiological conditions.…”